We propose to study the pharmacological aspects of ion and macromolecular secretion in the rat submaxillary gland in vivo. The pharmacological aspects of submaxillary secretion will be evaluated in terms of (1) the receptor mediated, physiological response to cholinergic and adrenergic agonists. This will be accomplished by determining the amount of K and 14C-glucosamine-mucin released into the cell suspension medium following stimulation by cholinergic and adrenergic agonists. (2) The changes in the concentration of cyclic AMP and cyclic GMP in these cells following stimulation by cholinergic and adrenergic agonists will then be correlated with the receptor mediated, physiological response of these cells with and without the addition of phosphodiesterase inhibitors; 3-isobutyl-1-methyl-xanthine and theophylline. (3) The effects of cholinergic and adrenergic mediated response on the metabolism of calcium in these cells. The rate of influx and efflux of calcium prior to and after stimulation by cholinergic and adrenergic agonists will be studied. The changes in calcium metabolism will then be correlated with the changes in the cyclic nucleotide levels and with the receptor mediated, physiological response of these cells following stimulation. These studies are intended to improve our understanding of the membrane mediated events and subsequent intracellular events that are thought to be important in the stimulus-secretion coupling mechanism.